Structure of Protein Involved in Aging and Cancer Solved
Telomerase structure resembles some viral enzymes
THURSDAY, Sept. 4 (HealthDay News) -- The three-dimensional structure of the telomerase enzyme, which is necessary to maintain proper chromosome length and is implicated in cancer and aging, has been solved and resembles some viral enzymes, according to the results of a study published online Aug. 31 in Nature.
Andrew J. Gillis, and colleagues from the Wistar Institute in Philadelphia, solved the three-dimensional structure of the catalytic subunit of Tribolium castaneum telomerase. The enzyme functions by using an RNA template to elongate DNA at the end of chromosomes, which normally become shorter with each cell division, they note.
The researchers found that the protein formed a ring-like structure with similarities to retroviral reverse transcriptases, viral RNA polymerases and B-family DNA polymerases. The interior of the ring contained elements implicated in binding and catalysis and was large enough to accommodate seven to eight bases of double-stranded DNA or RNA. The model showed that a DNA-RNA molecule, the expected substrate, would fit well in the interior of the ring and the DNA was properly positioned for elongation.
"The structure presented here provides a view of the full-length catalytic subunit of telomerase," Gillis and colleagues conclude. "Moreover, because telomerase has a critical role in both cancer and aging, these findings could potentially assist our efforts to identify and develop inhibitors and/or activators of this enzyme for the treatment of cancer and aging, respectively."